COL2A1 p.Cys86Ter
c.258C>A · rs794727261 · VCV195148
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 2 of 54 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.8 | GERP -0.21, phastCons 1 |
| Overall | ||
| CADD | 36.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- COL2A1
- Protein
- p.Cys86Ter
- Coding
- c.258C>A
- MANE Select
- NM_001844
- dbSNP
- rs794727261
- Type
- single nucleotide variant
- Location
- chr12:47999953 (GRCh38)
- Gene constraint
- LOEUF 0.183 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 53.56 · 11 PDB
- Residue 86
- the vwfc domain
Disease context
spondyloepiphyseal dysplasia, Stanescu type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: Stickler syndrome type 1multiple epiphyseal dysplasia, Beighton typeLegg-Calve-Perthes diseaseplatyspondylic dysplasia, Torrance typeKniest dysplasiaspondyloepiphyseal dysplasia congenitaspondyloepimetaphyseal dysplasia, Strudwick typeachondrogenesis type IIspondyloperipheral dysplasiamild spondyloepiphyseal dysplasia due to COL2A1 mutation with early-onset osteoarthritisspondyloepiphyseal dysplasia with metatarsal shorteningStickler syndrome, type I, nonsyndromic ocularspondylometaphyseal dysplasiavitreoretinopathy with phalangeal epiphyseal dysplasiaavascular necrosis of femoral head, primary, 1
For Spondyloepiphyseal dysplasia, Stanescu type (Orphanet):
- Inheritance
- Autosomal dominant
- Onset
- Childhood
Similar variants
- COL2A1 p.Cys86Tyr Uncertain significance ★ ⚠ same residue
- COL2A1 c.1222-2A>G Pathogenic ★★ same condition
- COL2A1 c.1365+1G>A Pathogenic/Likely pathogenic ★★ same condition
- COL2A1 c.1420-1G>A Pathogenic ★★ same condition
- COL2A1 c.1420-2A>G Pathogenic/Likely pathogenic ★★ same condition
- COL2A1 c.1527+135G>A Pathogenic/Likely pathogenic ★★ same condition
- COL2A1 c.1527+1G>A Likely pathogenic ★★ same condition
- COL2A1 c.1581+1G>A Likely pathogenic ★★ same condition
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/col2a1-p-cys86ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown